Kitoun Camélia, Saidjalolov Saidbakhrom, Bouquet Delphine, Djago Fabiola, Remaury Quentin Blancart, Sargueil Bruno, Poinot Pauline, Etheve-Quelquejeu Mélanie, Iannazzo Laura
Université Paris Cité, CNRS, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Paris F-75006, France.
Institut de Chimie des Milieux et Matériaux de Poitiers IC2MP, Université de Poitiers, UMR 7285, Poitiers 86073, France.
ACS Omega. 2023 Jan 17;8(4):3850-3860. doi: 10.1021/acsomega.2c06135. eCollection 2023 Jan 31.
Aminoacyl- and peptidyl-tRNA are specific biomolecules involved in many biological processes, from ribosomal protein synthesis to the synthesis of peptidoglycan precursors. Here, we report a post-synthetic approach based on traceless Staudinger ligation for the synthesis of a stable amide bond to access aminoacyl- or peptidyl-di-nucleotide. A series of amino-acid and peptide ester phenyl phosphines were synthetized, and their reactivity was studied on a 2'-N di-nucleotide. The corresponding 2'-amide di-nucleotides were obtained and characterized by LC-HRMS, and mechanistic interpretations of the influence of the amino acid phenyl ester phosphine were proposed. We also demonstrated that enzymatic 5'-OH phosphorylation is compatible with the acylated di-nucleotide, allowing the possibility to access stable aminoacylated-tRNA.
氨酰基 - 和肽基 - tRNA是参与许多生物过程的特定生物分子，从核糖体蛋白质合成到肽聚糖前体的合成。在此，我们报告了一种基于无痕施陶丁格连接的合成后方法，用于合成稳定的酰胺键以获得氨酰基 - 或肽基 - 二核苷酸。合成了一系列氨基酸和肽酯苯基膦，并研究了它们对2'-N二核苷酸的反应性。通过液相色谱 - 高分辨率质谱法获得并表征了相应的2'-酰胺二核苷酸，并对氨基酸苯基酯膦的影响提出了机理解释。我们还证明了酶促5'-OH磷酸化与酰化二核苷酸兼容，从而有可能获得稳定的氨酰化 - tRNA。
